Gut Microbiota – A New Modifiable Risk Factor for Metabolic Disease

The human gut microbiota refers to the 100 trillion microbes that reside in the human colon. Not only are they astounding in their number, but also in their diversity – such is the variety in the make-up of our separate gut flora that researchers are now able to identify ‘microbiome fingerprints’ characteristic of each individual.

From infancy throughout life, the gut microbes develop and evolve under influence of environmental, nutritional, immune and other factors, such as the use of antibiotics. The mutualistic relationship of these bacteria with the host has long been recognized; indeed it is to the metabolic functions of these microbes to which we owe some of our digestive activity and production of vitamins B and K, not to mention the protection they offer against colonization by ‘bad’ bacteria. The gut microbiota have even been regarded as a metabolic organ due to their dynamic role in manipulating genetic and dietary factors to shape human health.

Since the recognition that disturbances in gut flora (dysbiosis) lie behind inflammatory bowel disease (IBD), immune and certain other problems, there has been a dramatic rise in the popularity of probiotics and prebiotics. However this article shall focus on newer and yet still nascent research that examines the relationship between gut flora and obesity-related disorders. The idea first surfaced around a decade ago, where a series of experiments investigating the ‘obese’ gut microbiota elucidated some of the processes by which gut flora modulates energy harvest, energy storage as triglycerides and energy expenditure via fatty acid oxidation in the small intestine.

Comparing the gut microbiota of lean and obese individuals, researchers in France reported considerable differences in the levels of the most common types of gut bacteria. In obese subjects, levels of Bacteroides turned out to be much lower and those of Firmicutes, higher than in healthy subjects. Another study in Turkey in 2014 came up with similar findings, and also found a link between metabolic variables (such as blood sugar level and BMI) and altered levels of certain bacterial species.

As with every link that must stand up to examination, however, it remains to be said whether there is a causal relationship between gut microbiota and cardio-metabolic disease, or whether the disease itself alters composition of microbiota, hence making disturbed flora a marker for disease. Partly answering this question, studies have looked into how diet itself shapes gut flora. High-fat, low-fibre diets, consisting of highly processed foods have been linked with a poor and less diverse gut microbiota. A particular strain, Akkermansiamuciniphila which is associated with a healthy fibre-rich diet has also now been linked with lower levels of blood sugar, insulin and fats, and with a better metabolic profile.

The link between gut bacteria and levels of triglycerides and HDL cholesterol has been firmly established. State-of-the-art deep sequencing technology has been employed to identify at least 34 different types of bacteria that are intricately involved in lipid metabolism. Two key mechanisms of this interaction between microbiota and host have been delineated: modification of bile acids in the gut, and production of short chain fatty acids by bacteria.

In the gut, bile acids along with host hepatic enzymes interact in complex ways to promote digestion and absorption of dietary lipids. Researchers have now identified a bacterial protein product, bile salt hydrolase that chemically alters bile acids, in effect reducing serum cholesterol and weight gain, at least in rat test subjects.

Short chain fatty acids (SCFA) are produced as a result of fermentation of dietary fibre by the gut microbiota. SCFA are known to favorably impact energy homeostasis and metabolism in adipose tissue, skeletal muscle and liver, and therefore protect against insulin resistance and metabolic syndrome.

These latest findings, and the emboldening knowledge that the gut microbiota are a modifiable causative risk factor in obesity, type II diabetes and cardiovascular diseases, pave the way for new therapeutic strategies to be explored. Researchers are hinting at the promise of probiotics and even potential of fecal transplants in manipulating our gut flora. Some lessons that have already been learnt the hard way are repeated; antibiotic overuse kills, whilst increasing daily fibre intake promotes good obesity-staving bacteria like A. muciniphila.

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